The purpose of the proposed program is to provide pre- and post-doctoral training in mechanistically based quantitative toxicology to quantify individuals for research and teaching positions in universities and medical institutions, or research positions in national laboratories and other governmental agencies. Because of the uniqueness of the proposed training program in quantitative toxicology and its potential application in science-based risk assessment, it is conceivable that our trainees will be sought after by industry as well. The major research emphasis is toxicologic interactions of chemicals and physical agents. The endpoints to be studied are mutagenesis and carcinogenesis. Mechanistic studies will be integrated with physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) modeling and biologically based dose response (BBDR) modeling. Predoctoral trainees will enter the program with bachelor or masters' degree in biology, biochemistry, or chemistry. Exceptional candidates in physics, mathematics, or engineering interested in pursuing an advanced training in toxicology will be considered as well. They will be selected on the basis of their personal goals, past academic performance, scores on the Graduate Record Examination, and letters of recommendation. In those exceptional cases, where deficiencies in biology or other disciplines exist, remedial course work will be completed in the first year. Candidates considered for post-doctoral positions will include individuals with Ph.D., M.D., D.V.M. degrees. They must demonstrate meritorious academic work, have letters of reference attesting to their motivation, competence, and past research performance, and aspire to a research and/or teaching career related to toxicology. Candidates who are presently in a post-doctoral position with exceptional molecular biology skills and knowledge may be considered for re-training in quantitative toxicology to broadening their skills. This application requests support for 10 predoctoral and 5 post-doctoral traineeships.